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Background Physician shortages are prevalent in medically underserved areas, where healthcare disparities hinder physician recruitment and retention. The Hawai‘i Pacific Health (HPH) Summer Student Research Program (SSRP) provides early clinical and research experiences to pre-med students from Hawai’i, potentially enhancing their qualifications, supporting medical school acceptance rates, and fostering commitment to practicing in Hawai’i. Objective To evaluate the association between SSRP participation and medical school admissions, career trajectories, and retention of healthcare professionals in Hawai‘i, a medically underserved region. Methods A 38-year retrospective analysis examined 393 SSRP alumni (1986–2023), tracking educational and career outcomes, such as medical school admission, residency, and practice location, through surveys and internet research. Results The program was associated with a 73% medical school admission rate. Of 393 alumni, 221 became physicians, with 74 practicing in Hawai‘i. Among those in training, 81% expressed plans to practice locally. The program produced 57 abstracts, 43 posters, 53 oral presentations, and 37 peer-reviewed publications while providing students with clinical exposure and physician mentorship. Conclusion Community-based SSRPs may support the recruitment, retention, and cultivation of local students for medical careers and potentially bolster the physician workforce in underserved regions like Hawai‘i. By embedding clinical and research experiences within the community, the program is associated with enhanced medical school admissions and may foster long-term physician retention, including subspecialists, in the local healthcare system. This community-engaged approach contributes to medical education literature and provides a replicable model for other underserved areas to build sustainable healthcare workforces.

Telehealth visits increase patients' access to care and are often rated as \"just as good\" as face-to-face visits by oncology patients. Telehealth visits have become increasingly more common in the care of patients with cancer since the advent of the COVID-19 pandemic. Asians and Pacific Islanders are two of the fastest growing racial groups in the United States, but there are few studies assessing patient satisfaction with telemedicine among these two racial groups. Our objective was to compare satisfaction with communication during telehealth visits versus face-to-face visits among oncology patients, with a specific focus on Asian patients and Native Hawaiian and other Pacific Islander (NHOPI) patients. We surveyed a racially diverse group of patients who were treated at community cancer centers in Hawaii and had recently experienced a face-to-face visit or telehealth visit. Questions for assessing satisfaction with patient-physician communication were adapted from a previously published study of cancer survivors. Variables that impact communication, including age, sex, household income, education level, and cancer type and stage, were captured. Multivariable logistic models for patient satisfaction were created, with adjustments for sociodemographic factors. Participants who attended a face-to-face visit reported higher levels of satisfaction in all communication measures than those reported by participants who underwent a telehealth encounter. The univariate analysis revealed lower levels of satisfaction during telehealth visits among Asian participants and NHOPI participants compared to those among White participants for all measures of communication (eg, when asked to what degree \"[y]our physician listened carefully to you\"). Asian patients and NHOPI patients were significantly less likely than White patients to strongly agree with the statement (P<.004 and P<.007, respectively). Racial differences in satisfaction with communication persisted in the multivariate analysis even after adjusting for sociodemographic factors. There were no significant racial differences in communication during face-to-face visits. Asian patients and NHOPI patients were significantly less content with patient-physician communication during telehealth visits when compared to White patients. This difference among racial groups was not seen in face-to-face visits. The observation that telehealth increases racial disparities in health care satisfaction should prompt further exploration.

Background Chronic lung disease of prematurity (CLD) is the most prevalent complication of preterm birth and indicates an increased likelihood of long-term pulmonary complications. The accurate diagnosis of this condition is critical for long-term health management. Numerous definitions define CLD with different clinical parameters and radiology findings, making diagnosis of the disease ambiguous and potentially inaccurate. Methods 95 patients were identified for this study, as determined by the diagnosis or confirmation of CLD in the impression of the radiologist’s report on chest x-ray. Pulmonary function and complications were recorded at multiple benchmark timeframes within each patient’s first few months of life and used for determining eligibility under each definition. Results Each clinical definition of CLD had a high sensitivity for patients identified to have CLD by radiologists, correctly fitting over 90% of patients. Most patients included required invasive mechanical ventilation or positive pressure ventilation at 36 weeks postmenstrual age, indicating patients with radiographically confirmed CLD tended to have more severe disease. Radiologists tended to diagnose CLD before 36 weeks postmenstrual age, a timepoint used by multiple standard clinical definitions, with cases called earlier fitting under a larger percentage of definitions than those called later. Conclusions Radiologists tend to diagnose CLD in young patients with severe respiratory compromise, and can accurately diagnose the condition before developmental milestones for clinical definitions are met.

Elective sigmoid colectomy for recurrent uncomplicated diverticulitis remains controversial and is decided on an individual basis. Eighty patients treated conservatively (44 patients) or by elective surgery (36 patients) for recurrent uncomplicated diverticulitis were contacted and assessed for quality of life. The mean difference in quality of life scores was greater after surgery (overall + 2.14%, laparoscopic resection +4.95%, p = 0.36 and p = 0.11, respectively) as compared to conservative management. Female patients undergoing laparoscopic resection had statistically significantly higher quality of life scores than women treated conservatively (+8.98%; p = 0.049). Twenty-eight of 29 responding patients stated that they were highly satisfied and would have the operation done again. Elective sigmoidectomy is a valid treatment option for recurrent uncomplicated diverticulitis in terms of quality of life. Quality of life improved most if surgery was performed laparoscopically, especially in women.

Noncoding genetic variation drives phenotypic diversity, but underlying mechanisms and affected cell types are incompletely understood. Here, investigation of effects of natural genetic variation on the epigenomes and transcriptomes of Kupffer cells derived from inbred mouse strains identified strain-specific environmental factors influencing Kupffer cell phenotypes, including leptin signaling in Kupffer cells from a steatohepatitis-resistant strain. Cell-autonomous and non-cell-autonomous effects of genetic variation were resolved by analysis of F1 hybrid mice and cells engrafted into an immunodeficient host. During homeostasis, non-cell-autonomous trans effects of genetic variation dominated control of Kupffer cells, while strain-specific responses to acute lipopolysaccharide injection were dominated by actions of cis -acting effects modifying response elements for lineage-determining and signal-dependent transcription factors. These findings demonstrate that epigenetic landscapes report on trans effects of genetic variation and serve as a resource for deeper analyses into genetic control of transcription in Kupffer cells and macrophages in vitro. The mechanisms by which noncoding genetic variation shapes tissue macrophage phenotypic diversity remain obscure. Glass and colleagues define cell-intrinsic and environmental effects contributing to genetic control of Kupffer cell transcription.

Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, while lung ADC exhibits significant glucose independence. Clinically, elevated GLUT1-mediated glycolysis in lung SqCC strongly correlates with high 18 F-FDG uptake and poor prognosis. This previously undescribed metabolic heterogeneity of NSCLC subtypes implicates significant potential for the development of diagnostic, prognostic and targeted therapeutic strategies for lung SqCC, a cancer for which existing therapeutic options are clinically insufficient. Adenocarcinoma and squamous cell carcinoma are distinct subtypes of non-small cell lung cancer. Here, the authors show that increased glycolytic flux, via increased glucose transporter Glut1 expression, is a core metabolic feature of squamous cell carcinoma that renders it sensitive to glycolysis inhibition.

Background The metabolism of archaeal methanogens drives methane release into the environment and is critical to understanding global carbon cycling. Methanogenesis operates at a very low reducing potential compared to other forms of respiration and is therefore critical to many anaerobic environments. Harnessing or altering methanogen metabolism has the potential to mitigate global warming and even be utilized for energy applications. Results Here, we report draft genome sequences for the isolated methanogens Methanobacterium bryantii , Methanosarcina spelaei , Methanosphaera cuniculi , and Methanocorpusculum parvum . These anaerobic, methane-producing archaea represent a diverse set of isolates, capable of methylotrophic, acetoclastic, and hydrogenotrophic methanogenesis. Assembly and analysis of the genomes allowed for simple and rapid reconstruction of metabolism in the four methanogens. Comparison of the distribution of Clusters of Orthologous Groups (COG) proteins to a sample of genomes from the RefSeq database revealed a trend towards energy conservation in genome composition of all methanogens sequenced. Further analysis of the predicted membrane proteins and transporters distinguished differing energy conservation methods utilized during methanogenesis, such as chemiosmotic coupling in Msar. spelaei and electron bifurcation linked to chemiosmotic coupling in Mbac. bryantii and Msph. cuniculi . Conclusions Methanogens occupy a unique ecological niche, acting as the terminal electron acceptors in anaerobic environments, and their genomes display a significant shift towards energy conservation. The genome-enabled reconstructed metabolisms reported here have significance to diverse anaerobic communities and have led to proposed substrate utilization not previously reported in isolation, such as formate and methanol metabolism in Mbac. bryantii and CO 2 metabolism in Msph. cuniculi . The newly proposed substrates establish an important foundation with which to decipher how methanogens behave in native communities, as CO 2 and formate are common electron carriers in microbial communities.

Changes in gene regulation underlie much of phenotypic evolution 1 . However, our understanding of the potential for regulatory evolution is biased, because most evidence comes from either natural variation or limited experimental perturbations 2 . Using an automated robotics pipeline, we surveyed an unbiased mutation library for a developmental enhancer in Drosophila melanogaster . We found that almost all mutations altered gene expression and that parameters of gene expression—levels, location, and state—were convolved. The widespread pleiotropic effects of most mutations may constrain the evolvability of developmental enhancers. Consistent with these observations, comparisons of diverse Drosophila larvae revealed apparent biases in the phenotypes influenced by the enhancer. Developmental enhancers may encode a higher density of regulatory information than has been appreciated previously, imposing constraints on regulatory evolution. A robotic pipeline is used to survey a library of mutations in a Drosphila gene enhancer, showing that most mutations altered gene expression and had widespread pleiotropic effects that are likely to constrain regulatory evolution.

This article focuses on the numerical solution of a time-dependent parabolic problem that exhibits singular perturbations and involves two perturbation parameters. To address this problem, a fitted mesh finite difference method is developed. In numerical discretization, the implicit Crank-Nicolson technique is employed to discretize the time derivative using a uniform mesh. As for the spatial derivative, a hybrid finite difference scheme known as the adaptive fitted mesh of the Shishkin type is utilized. The study also includes a discussion on a priori bounds for the continuous solution and its derivatives. The proposed method is proven to be uniformly convergent of order two in both time and space. Theoretical analysis and simulations on various test examples confirm the scheme’s accuracy and convergence properties.